Purpose

To determine the feasibility, safety, and tolerability of concomitant chemoradiotherapy administered at standard doses in HIV-infected women with locally-advanced cervical cancer (LACC) receiving antiretroviral therapy (ART).

Patients and methods

Eligible participants had HIV infection and untreated, histologically-confirmed, invasive carcinoma of the uterine cervix, FIGO stages IB2, IIA (if tumor >4 cm), IIB, IIIA, IIIB, or IVA and met standard eligibility criteria. Subjects were prescribed 41.4-45 Gy external beam radiation therapy followed by high dose rate brachytherapy concomitant with up to six weekly doses of cisplatin 40 mg/m2 and were followed for 12 months.

Results

Sixty-four women were screened at two sites in sub-Saharan Africa, of whom 40 eligible participants were enrolled, for a screening ratio of 1.60. Of the 38 eligible participants who initiated study treatment, 31 (82%) completed treatment. By the 12-month follow-up visit, 7 women had died of disease and 29 of 31 (94%) returned for follow-up. One-year progression-free survival was 76.3% (95% CI, 59.4-86.9%), and did not significantly differ according to stage at entry (p = 0.581). Participant-reported adherence to ART was high; by 12 months, 93% of participants had an undetectable viral load. The most common grade 3 or 4 adverse event was decreased lymphocyte count that affected all treated participants. Non-hematologic serious adverse events were similar to those observed in women with LACC without HIV infection.

Conclusions

The majority of HIV-infected women with LACC can complete concomitant chemoradiotherapy with the same cisplatin dose used in HIV-uninfected women with comparable tolerability and high ART adherence while on treatment.

Purpose

Given the increasing availability of radiation therapy in sub-Saharan Africa, clinical trials that include radiation therapy are likely to grow. Ensuring appropriate delivery of radiation therapy through rigorous quality assurance is an important component of clinical trial execution. We reviewed the process for credentialing radiation therapy sites and radiation therapy quality assurance through the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center for AIDS Malignancy Consortium (AMC)-081, a multicenter study of cisplatin and radiation therapy for women with locally advanced cervical cancer living with HIV, conducted by the AIDS Malignancy Consortium at 2 sites in South Africa and Zimbabwe.

Methods and materials

Women living with HIV with newly diagnosed stage IB2, IIA (>4 cm), IIB-IVA cervical carcinoma (per the 2009 International Federation of Gynecology and Obstetrics [FIGO] staging classifications) were enrolled in AMC-081. They received 3-dimensional conformal external beam radiation therapy (EBRT) to the pelvis (41.4-45 Gy) using a linear accelerator, high-dose-rate brachytherapy (6-9 Gy to point A with each fraction and up to 4 fractions), and concurrent weekly cisplatin (40 mg/m²). IROC reviewed EBRT and brachytherapy quality assurance records after treatment.

Results

All of the 38 women enrolled in AMC-081 received ±5% of the protocol-specified prescribed dose of EBRT. Geometry of brachytherapy applicator placement was scored as per protocol in all implants. Doses to points A and B, International Commission on Radiation Units and Measurements (ICRU) bladder, or ICRU rectum required correction by IROC in >50% of the implants. In the final evaluation, 58% of participants (n = 22) were treated per protocol, 40% (n = 15) had minor protocol deviations, and 3% (n = 1) had major protocol deviations. No records were received within 60 days of treatment completion as requested in the protocol.

Conclusions

Major radiation therapy deviations were low, but timely submission of radiation therapy data did not occur. Future studies, especially those that include specialized radiation therapy techniques such as stereotactic or intensity-modulated radiation therapy, will require pathways to ensure timely and adequate quality assurance.

BACKGROUND: Anal high-grade squamous intraepithelial lesions (HSILs) ablation may reduce the incidence of invasive cancer, but few data exist on treatment efficacy and natural regression without treatment. METHODS: An open-label, randomized, multisite clinical trial of human immunodeficiency virus (HIV)-infected adults aged ≥27 years with 1-3 biopsy-proven anal HSILs (index HSILs) without prior history of HSIL treatment with infrared coagulation (IRC). Participants were randomized 1:1 to HSIL ablation with IRC (treatment) or no treatment (active monitoring [AM]). Participants were followed every 3 months with high-resolution anoscopy. Treatment participants underwent anal biopsies of suspected new or recurrent HSILs. The AM participants underwent biopsies only at month 12. The primary end point was complete clearance of index HSIL at month 12. RESULTS: We randomized 120 participants. Complete index HSIL clearance occurred more frequently in the treatment group than in the AM (62% vs 30%; risk difference, 32%; 95% confidence interval [CI], 13%-48%; P < .001). Complete or partial clearance (clearance of ≥1 index HSIL) occurred more commonly in the treatment group (82% vs 47%; risk difference, 35%; 95% CI, 16%-50%; P < .001). Having a single index lesion, compared with having 2-3 lesions, was significantly associated with complete clearance (relative risk, 1.96; 95% CI, 1.22-3.10). The most common adverse events related to treatment were mild or moderate anal pain and bleeding. No serious adverse events were deemed related to treatment or study participation. CONCLUSION: IRC ablation of anal HSILs results in more clearance of HSILs than observation alone.

OBJECTIVE: To evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal intraepithelial neoplasia (PAIN) and vulvar intraepithelial neoplasia (VIN) lesions in HIV-positive individuals. DESIGN: Phase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium. METHODS: : HIV-positive patients with biopsy-proven high-grade PAIN that was at least 3 cm were enrolled. PAIN biopsy specimens were assessed for human papillomavirus (HPV) using PCR and type-specific HPV probing. Participants applied 1% topical cidofovir to PAIN and VIN (if present) for six 2-week cycles. Results were designated as complete response (CR), partial response (PR) (>50% reduction in size), stable disease, or progressive disease (PD). RESULTS: Twenty-four men and nine women (eight with high-grade VIN as well) were enrolled. Mean age was 44 years and mean CD4 cell count was 412 cells/μl. HPV DNA (most commonly HPV16) was detected in all pretreatment study specimens. Twenty six (79%) participants completed treatment per protocol: CR, five (15%); PR, 12 (36%), stable disease, seven (21%); PD, two (6%) (one with a superficially invasive cancer and one with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 patients) and ulceration (13 patients). CONCLUSION: Topical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed.

Purpose

High-grade anal intraepithelial neoplasia (HGAIN) is the precursor lesion to invasive anal cancer. Human papillomavirus (HPV) vaccination holds great promise for preventing anal cancer.

Methods

We examined 235 HIV-1-infected men screening for participation in a multisite clinical trial of a quadrivalent HPV vaccine. All participants had anal swabs obtained for HPV testing and cytology and high-resolution anoscopy with biopsies of visible lesions to assess for HGAIN.

Results

HPV types 16 and 18 were detected in 23% and 10%, respectively; abnormal anal cytology was found in 56% and HGAIN in 30%. HGAIN prevalence was significantly higher in those with HPV16 detection compared to those without (38% vs 17%; P = .01). Use of antiretroviral therapy and nadir and current CD4+ cell count were not associated with abnormal anal cytology or HGAIN.

Conclusion

HGAIN is highly prevalent in HIV-infected men. Further studies are needed on treatment and prevention of HGAIN.

Objective

To evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal intraepithelial neoplasia (PAIN) and vulvar intraepithelial neoplasia (VIN) lesions in HIV-positive individuals.

Design

Phase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium.

Methods

: HIV-positive patients with biopsy-proven high-grade PAIN that was at least 3 cm were enrolled. PAIN biopsy specimens were assessed for human papillomavirus (HPV) using PCR and type-specific HPV probing. Participants applied 1% topical cidofovir to PAIN and VIN (if present) for six 2-week cycles. Results were designated as complete response (CR), partial response (PR) (>50% reduction in size), stable disease, or progressive disease (PD).

Results

Twenty-four men and nine women (eight with high-grade VIN as well) were enrolled. Mean age was 44 years and mean CD4 cell count was 412 cells/μl. HPV DNA (most commonly HPV16) was detected in all pretreatment study specimens. Twenty six (79%) participants completed treatment per protocol: CR, five (15%); PR, 12 (36%), stable disease, seven (21%); PD, two (6%) (one with a superficially invasive cancer and one with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 patients) and ulceration (13 patients).

Conclusion

Topical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed.

It is well established that persons living with HIV (PLWH) have highly elevated rates of anal HSIL and anal cancer compared with those who are not living with HIV. The 5-year risk of anal cancer following anal HSIL has been reported to be as high as 14.1% among PLWH compared with 3.2% among those who are not living with HIV. To address these concerns, the AIDS Malignancy Consortium completed a large-scale, randomized trial to compare strategies for the prevention of anal cancer among PLWH with anal HSIL. The objective of the study was to determine whether treating anal HSIL was effective in reducing the incidence of anal cancer in PLWH compared with active monitoring. This paper describes the design of the ANal Cancer/HSIL Outcomes Research Study (ANCHOR) with respect to estimating the anal cancer event rate in this high risk population.

Background

Anal high-grade squamous intraepithelial lesions (HSILs) ablation may reduce the incidence of invasive cancer, but few data exist on treatment efficacy and natural regression without treatment.

Methods

An open-label, randomized, multisite clinical trial of human immunodeficiency virus (HIV)-infected adults aged ≥27 years with 1-3 biopsy-proven anal HSILs (index HSILs) without prior history of HSIL treatment with infrared coagulation (IRC). Participants were randomized 1:1 to HSIL ablation with IRC (treatment) or no treatment (active monitoring [AM]). Participants were followed every 3 months with high-resolution anoscopy. Treatment participants underwent anal biopsies of suspected new or recurrent HSILs. The AM participants underwent biopsies only at month 12. The primary end point was complete clearance of index HSIL at month 12.

Results

We randomized 120 participants. Complete index HSIL clearance occurred more frequently in the treatment group than in the AM (62% vs 30%; risk difference, 32%; 95% confidence interval [CI], 13%-48%; P < .001). Complete or partial clearance (clearance of ≥1 index HSIL) occurred more commonly in the treatment group (82% vs 47%; risk difference, 35%; 95% CI, 16%-50%; P < .001). Having a single index lesion, compared with having 2-3 lesions, was significantly associated with complete clearance (relative risk, 1.96; 95% CI, 1.22-3.10). The most common adverse events related to treatment were mild or moderate anal pain and bleeding. No serious adverse events were deemed related to treatment or study participation.

Conclusion

IRC ablation of anal HSILs results in more clearance of HSILs than observation alone.

OBJECTIVE:The aim of the study was to develop recommended techniques and quality assurance metrics for the practice of Digital Anal Rectal Examination (DARE). MATERIALS AND METHODS:The International Anal Neoplasia Society undertook a literature review and, using the AGREE II technique, developed guidelines for performing DARE. RESULTS:A consensus was formed regarding the optimum conditions and characteristics of DARE. Several Quality Assurance metrics were developed. CONCLUSIONS:Digital Anal Rectal Examination is a cheap and potentially universally available technique, which has the potential to facilitate the early diagnosis of anal cancers, when they are most amenable to treatment. These guidelines provide a basis for teaching the technique and may be used as for evaluation research.

BACKGROUND: Women living with human immunodeficiency virus (WLHIV) have disproportionately high rates of squamous cell carcinoma of the anus compared with the general population of women. Anal high-grade squamous intraepithelial lesions (HSILs) precede anal cancer, and accurate studies of HSIL prevalence among WLHIV in the United States are lacking. METHODS: The AIDS Malignancy Consortium 084 study was a multicenter national trial to evaluate the prevalence of and risk factors for anal HSIL in a US cohort. Eligible participants were WLHIV aged ≥18 years with no history of anal HSIL. Study participants had an examination including collection of cervical/vaginal and anal specimens, followed by high-resolution anoscopy with biopsy. RESULTS: We enrolled 256 women with evaluable anal pathology. The mean age was 49.4 years, 64% women were non-Hispanic black, 67% were former or current smokers, and 56% reported ever having anal sex with a man. The median CD4 T-cell count was 664 cells/μL. The prevalence of anal histologic HSIL (hHSIL) was 27% (95% confidence interval [CI], 22%-33%). There was a strong concordance (240/254) between local and consensus pathologists for hHSIL vs less than hHSIL (κ = 0.86 [95% CI, .79-.93]). Current CD4 count of ≤200 cells/μL was the strongest predictor of consensus anal hHSIL diagnosis (adjusted odds ratio [aOR], 10.34 [95% CI, 3.47-30.87]). History of anoreceptive intercourse was also associated with hHSIL (aOR, 2.44 [95% CI, 1.22-4.76]). CONCLUSIONS: The prevalence of anal hHSIL in WLHIV in the United States was 27% in this study where all participants received high-resolution anoscopy and biopsy.